The objective of this study is to understand better the crossbridge cycle in striated muscle and to shed light upon the physical chemical steps by which crossbridges transduce chemical energy into mechanical work. To do this I propose to perturb the normal crossbridge cycle in single intact and skinned frog muscle fibers with deuterium oxide (D2O), and with changes in ionic strength, myofilament spacing, and bathing solution tonicity, and to observe the consequences of these perturbations on the relation between muscle force and velocity of shortening. D2O is thought to slow the detachment of crossbridges from the thin filament and may alter the force exerted by each crossbridge as well. Changes in ionic strength primarily affect the crossbridge attachment step. Ionic strength will be altered directly for skinned fibers and indirectly for intact fibers through changes in tonicity. Alterations in myofilament spacing (and thereby in the crossbridge working distance) appear to influence tension generation but it is not known which step of the cycle is affected. Myofilament spacing will be altered by changing overall fiber size of the skinned fibers with long-chain polymers and of the intact fibers with changes in tonicity or in the KxCl product of the bathing solution. Alterations of excitation-contraction coupling and of calcium release will be counteracted with caffeine, zinc, nitrate or dantrolene sodium, in order to study crossbridge kinetics under conditions of constant calcium. The steps of crossbridge cycle which are affected by these perturbations will be determined by fitting mathematical model of the cycle to the force-velocity data. The proposed study will enlarge our understanding of the mechanism basic to contraction, not only of skeletal muscle, but to that of cardiac and smooth muscle as well.